Anxiolytic effects of dopamine receptor ligands: I. Involvement of dopamine autoreceptors.
The anxiolytic-like properties of dopamine agonists and antagonists with different receptor profiles were investigated in the ultrasonic vocalization test in rats after subcutaneous administration. Only dopamine D2 receptor agonists inhibited ultrasonic vocalization with the following ED50 values: apomorphine (0.07 mg/kg), quinelorane (0.01 mg/kg), quinpirole (0.04 mg/kg), pramipexole (0.09 mg/kg), roxindole (0.04 mg/kg), talipexole (0.04 mg/kg), (+/-)-7-OH-DPAT (0.05 mg/kg), (+/-)-PPHT (0.03 mg/kg), (-)-TNPA (0.06 mg/kg), PD128907 (0.13 mg/kg). The D2 antagonists haloperidol, mazapertine, raclopride, remoxipride, L745870, U99194A, U101958 and S(-)-DS121, the partial agonists PD143188 and preclamol, the selective D1 agonist R(+)-SKF38393 and the D1 antagonist SCH23390, and the uptake inhibitors GBR12909, GBR12935 and indatraline lacked significant inhibitory effects on ultrasonic vocalization. Because at least some of the D2 receptor agonists investigated have selectivity for dopamine autoreceptors, it is speculated that the dopamine autoreceptor may be a target for the development of new antianxiety drugs.
Bartoszyk
G D
GD
Merck KGaA, Department of CNS Research, Darmstadt, Germany. Gerd.Bartoszyk@merck.de
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology*; D017660:Autoreceptors / Q000187:drug effects* / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D014828:Vocalization, Animal / Q000187:drug effects
D014151:Anti-Anxiety Agents; D017660:Autoreceptors; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D008024:Ligands; D014179:Neurotransmitter Uptake Inhibitors; D017448:Receptors, Dopamine D2; D003975:Diazepam